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Identification of HIV transmitting CD11c+ human epidermal dendritic cells

Lookup NU author(s): Dr Rachel Botting, James Fletcher, Professor Muzlifah Haniffa

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2019, The Author(s). Langerhans cells (LC) are thought to be the only mononuclear phagocyte population in the epidermis where they detect pathogens. Here, we show that CD11c+ dendritic cells (DCs) are also present. These cells are transcriptionally similar to dermal cDC2 but are more efficient antigen-presenting cells. Compared to LCs, epidermal CD11c+ DCs are enriched in anogenital tissues where they preferentially interact with HIV, express the higher levels of HIV entry receptor CCR5, support the higher levels of HIV uptake and replication and are more efficient at transmitting the virus to CD4 T cells. Importantly, these findings are observed using both a lab-adapted and transmitted/founder strain of HIV. We also describe a CD33low cell population, which is transcriptionally similar to LCs but does not appear to function as antigen-presenting cells or acts as HIV target cells. Our findings reveal that epidermal DCs in anogenital tissues potentially play a key role in sexual transmission of HIV.


Publication metadata

Author(s): Bertram KM, Botting RA, Baharlou H, Rhodes JW, Rana H, Graham JD, Patrick E, Fletcher J, Plasto TM, Truong NR, Royle C, Doyle CM, Tong O, Nasr N, Barnouti L, Kohout MP, Brooks AJ, Wines MP, Haertsch P, Lim J, Gosselink MP, Ctercteko G, Estes JD, Churchill MJ, Cameron PU, Hunter E, Haniffa MA, Cunningham AL, Harman AN

Publication type: Article

Publication status: Published

Journal: Nature Communications

Year: 2019

Volume: 10

Issue: 1

Online publication date: 21/06/2019

Acceptance date: 24/05/2019

Date deposited: 08/07/2019

ISSN (electronic): 2041-1723

Publisher: Nature Publishing Group

URL: https://doi.org/10.1038/s41467-019-10697-w

DOI: 10.1038/s41467-019-10697-w


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Funding

Funder referenceFunder name
HHSN261200800001E
WT107931/Z/15/Z

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